Low-dose versus standard-dose ritonavir-boosted atazanavir in virologically suppressed Thai adults with HIV (LASA): a randomised, open-label, non-inferiority trial

Bunupuradah, Torsak, Kiertiburanakul, Sasisopin, Avihingsanon, Anchalee, Chetchotisakd, Ploenchan, Techapornroong, Malee, Leerattanapetch, Niramon, Kantipong, Pacharee, Bowonwatanuwong, Chureeratana, Banchongkit, Sukit, Klinbuayaem, Virat, Mekviwattanawong, Sripetcharat, Nimitvilai, Sireethorn, Jirajariyavej, Supunnee, Prasithsirikul, Wisit, Munsakul, Warangkana, Bhakeecheep, Sorakij, Chaivooth, Suchada, Phanuphak, Praphan, Cooper, David A., Apornpong, Tanakorn, Kerr, Stephen J., Emery, Sean and Ruxrungtham, Kiat (2016) Low-dose versus standard-dose ritonavir-boosted atazanavir in virologically suppressed Thai adults with HIV (LASA): a randomised, open-label, non-inferiority trial. Lancet HIV, 3 8: e343-e350. doi:10.1016/S2352-3018(16)30010-8


Author Bunupuradah, Torsak
Kiertiburanakul, Sasisopin
Avihingsanon, Anchalee
Chetchotisakd, Ploenchan
Techapornroong, Malee
Leerattanapetch, Niramon
Kantipong, Pacharee
Bowonwatanuwong, Chureeratana
Banchongkit, Sukit
Klinbuayaem, Virat
Mekviwattanawong, Sripetcharat
Nimitvilai, Sireethorn
Jirajariyavej, Supunnee
Prasithsirikul, Wisit
Munsakul, Warangkana
Bhakeecheep, Sorakij
Chaivooth, Suchada
Phanuphak, Praphan
Cooper, David A.
Apornpong, Tanakorn
Kerr, Stephen J.
Emery, Sean
Ruxrungtham, Kiat
Title Low-dose versus standard-dose ritonavir-boosted atazanavir in virologically suppressed Thai adults with HIV (LASA): a randomised, open-label, non-inferiority trial
Journal name Lancet HIV   Check publisher's open access policy
ISSN 2352-3018
2405-4704
Publication date 2016-08-01
Year available 2016
Sub-type Article (original research)
DOI 10.1016/S2352-3018(16)30010-8
Open Access Status Not yet assessed
Volume 3
Issue 8
Start page e343
End page e350
Total pages 7
Place of publication London, United Kingdom
Publisher The Lancet Publishing Group
Collection year 2017
Language eng
Formatted abstract
Background
Thai patients with HIV have higher exposure to HIV protease inhibitors than do white people and dose reduction might be possible. We compared the efficacy of low-dose with standard-dose ritonavir-boosted atazanavir in virologically suppressed Thai patients with HIV.

Methods
In this randomised, open-label, non-inferiority trial, we recruited patients aged 18 years or older who were receiving ritonavir-boosted protease-inhibitor-based antiretroviral therapy (ART) with HIV plasma viral loads of less than 50 copies per mL, an alanine aminotransferase concentration of less than 200 IU/L, and a creatinine clearance of at least 60 mL/min from 14 hospitals in Thailand. We excluded patients who had active AIDS-defining disease or opportunistic infections, had a history of an HIV viral load of 1000 copies per mL or more after 24 weeks of any ritonavir-boosted protease-inhibitor-based ART, used concomitant medications that could interact with the study drugs, were pregnant or lactating, had illnesses that might change the effect of the study drugs, or had a history of sensitivity to the study drugs. A biostatistician at the study coordinating centre randomly allocated patients (1:1) to switch the protease inhibitor for oral atazanavir 200 mg and ritonavir 100 mg or for atazanavir 300 mg and ritonavir 100 mg once daily, both with two nucleoside or nucleotide reverse transcriptase inhibitors at recommended doses. Randomisation was done with a minimisation schedule, stratified by recruiting centre, use of tenofovir, and use of indinavir as a component of the preswitch regimen. The primary endpoint was the proportion of patients with viral loads of less than 200 copies per mL at week 48, and we followed up patients every 12 weeks. Treatments were open label, the non-inferiority margin was −10%, and all patients who received at least one dose of study medication were analysed. This trial is registered with ClinicalTrials.gov, number NCT01159223.

Findings
Between July 6, 2011, and Dec 23, 2013, we randomly assigned 559 patients: 279 to receive atazanavir 200 mg and ritonavir 100 mg (low dose) and 280 to atazanavir 300 mg and ritonavir 100 mg (standard dose). At week 48, 265 (97·1%) of 273 in the low-dose group and 267 (96·4%) of 277 in the standard-dose group had viral loads of less than 200 copies per mL (difference 0·68; 95% CI −2·29 to 3·65). Seven (3%) of 273 in the low-dose group and 21 (8%) of 277 in the standard-dose group discontinued their assigned treatment (p=0·01). 46 (17%) of 273 participants in the low-dose group and 97 (35%) of 277 in the standard-dose group had total bilirubin grade 3 or higher toxicity (≥3·12 mg/dL; p<0·0001).

Interpretation
A switch to low-dose atazanavir should be recommended for Thai patients with well controlled HIV viraemia while on regimens based on boosted protease inhibitors.

Funding
The National Health Security Office and Kirby Institute for Infection and Immunity in Society.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Faculty of Medicine
 
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